Cosolvents water-miscible organic solvents

When the aqueous solubility of a drug is well below its therapeutic dose, a mixture of solvents is added to achieve sufLciently high solubility. Thus, a cosolvent is a water-miscible organic solvent... 

Partially water-miscible organic solvents (PMOSs) may act as either cosolvents or cosolutes, and the research in the past has shown flic complexity of their effects. " It was demonstrated that in order to exert effects on solubility or sorption of HOCs, PMOSs must exist as a component of the solvent mixture in an appreciable amount Munz and Roberts suggested a mole fi action of greater than 0.005 and Rao and coworkers proposed a volume percent of 1% or a concentration above lO mg/L. Cosolvents with relatively high water solubility are likely to demonstrate observable effects on the solubilities of solutes, up to their solubility limits, in a similar manner to cosolvents of complete miscibility with water. A few experimental examples of the effects of PMOSs include 1 -butanol and... 

Water-miscible organic solvents. These organic solvents are miscible with water at the temperature of the reaction. Any cosolvent system having 0-100% ratio of the solvent/ water ean be prepared from this kind of solvent. Note that some organic solvents having limited water solubility at ambient temperature, and hence are not regarded as water-miscible, beeome miseible at elevated temperature. 

In the following text, examples of solvent effects on enzyme selectivity, referred either to systems based (i) on water-miscible organic cosolvents added to aqueous buffers or (ii) on organic media with low water activity, are discussed. 

We conclude this section with some brief comments on the cosolvent effects of partially miscible organic solvents (PMOSs). These solvents include very polar liquids such as w-butanol, w-butanone, w-pentanol, or o-cresol, but also nonpolar organic compounds such as benzene, toluene, or halogenated methanes, ethanes, and ethenes. For the polar PMOS, a similar effect as for the CMOS can be observed that is, these solvents decrease the activity coefficient of an organic solute when added to pure water or to a CMOS/water mixture (Pinal et al., 1990 Pinal et al., 1991 Li and Andren, 1994). For the less polar PMOS there is not enough data available to draw any general conclusions. 

Cosolvent technology is similar to the surfactant enhancement technology. Instead of a surfactant, the injection well receives a solvent mixture (e.g., water plus a miscible organic solvent such as alcohol). The cosolvent mixture is injected up-gradient of the... 

CALB is an exceptionally robust protein which is deactivated only at 50-60°C, and thus also shows increased resistance towards organic solvents. In contrast to many other lipases, the enzyme appears to be rather rigid and does not show a pronounced effect of interfacial activation [430], which makes it an intermediate between an esterase and a lipase. This latter property is probably the reason why its selectivity could be predicted through computer modeling to a fair extent [431], and for the majority of substrates the Kazlauskas rule (Scheme 2.49) can be applied. In line with these properties of CALB, selectivity-enhancement by addition of water-miscible organic cosolvents such as t-butanol or acetone is possible - a technique which is rather common for esterases. All of these properties make CALB the most widely used lipase both in the hydrolysis [432-437] and synthesis of esters (Sect. 3.1.1). 

Lowering the water-activity of the medium [1565] by using water-miscible organic cosolvents such as ethanol or methanol. Alternatively, the reaction can be carried out in a biphasic aqueous-organic system or in a monophasic organic solvent (e.g., ethyl acetate, di-/-propyl, or methyl t-butyl ether) which contains only traces of water to preserve the enz3mie s activity. 

Lowering the water-activity (concentration) of the system by addition of water-miscible organic cosolvents. In this respect, polyhydroxy compounds such as glycerol or butane-1,4-diol have been shown to conserve enzyme activity better than the solvents which are more commonly employed, such as DMF, DMSO, ethanol, acetone, or acetonitrile [305]. Alternatively, peptide synthesis may also be performed with neat reactants - i.e., in the absence of solvents [306]. 

It is more difficult to evaluate the effects of cosolvents which have limited miscibility with water. These organic solvents have limited miscibility with water. In the literature, they have been termed as both cosolvents and cosolutes, and there is no clear criteria for the distinction. Cosolvent is usually miscible with water, or to be used in an attempt to increase the aqueous solubility of the solute. Cosolute, on the other hand, may be organic chemicals which have a similar chemical structure or behave similarly with the solute when they exist in water alone. The effects of cosolutes have been examined in a limited number of published papers. " ... 

Efficient biphasic catalysis relies on the rapid mass transfer across the aqueous and organic phases. As indicated, this poses a problem for higher olefins because of their insolubility in water. To tackle the issue and thus to increase the hydroformylation rates, additives, such as co-solvents, surfactants, or modified cyclodextrins, have been explored. A water-miscible organic cosolvent such as an alcohol could increase the solubility of alkenes in the aqueous phase or the catalyst in the organic phase. For example, using [Rh(p-S Bu)(CO)(m-TPPTS)]2 as a catalyst, hydroformylation of 1-octene gave less than 24% conversion after 15 h in water at 80 °C but it reached 90% conversion in 10 h in water/methanol (3 1) [28]. Using Rh-1, 1-dodecene was hydroformylated with 42% conversion to aldehydes in a mixture solvent of water/propanol, while no hydroformylation was observed at all in water alone under identical conditions [29]. The same trend was observed in the reaction of 1-octene catalyzed by Co/BiphTS (BiphTS, trisulfonated tris(biphenyl)phosphine) [30]. 

Miscible organic solutes modify the solvent properties of the solution to decrease the interfacial tension and give rise to an enhanced solubility of organic chemicals in a phenomenon often called cosolvency . According to theory, a miscible organic chemical such as a short chain alcohol will have the effect of modifying the structure of the water in which it is dissolved. On the macroscopic scale, this will manifest itself as a decrease in the surface tension of the solution [238,246]. 

Addition of a cosolvent is an alternative mechanism to increase contaminant solubility in an aqueous solution. When a contaminant with low solubility enters an aqueous solution containing a cosolvent (e.g., acetone), the logarithm of its solubility is nearly a linear function of the mole fraction composition of the cosolvent (Hartley and Graham-Bryce 1980). The amount of contaminant that can dissolve in a mixture of two equal amounts of different solvents, within an aqueous phase, is much smaller than the amount that can dissolve solely by the more powerful solvent. In the case of a powerful organic solvent miscible with water, a more nearly linear slope for the log solubility versus solvent composition relationship is obtained if the composition is plotted as volume fraction rather than mole fraction. 

Crystalline salts of many organic acids and bases often have a maximum solubility in a mixture of water and water-miscible solvents. The ionic part of snch a molecule requires a strongly polar solvent, snch as water, to initiate dissociation. A mixture of water-miscible solvents hydrates and dissociates the ionic fraction of pollutants at a higher concentration than wonld either solvent alone. Therefore, from a practical point of view, the deliberate nse of a water-soluble solvent as a cosolvent in the formnlation of toxic organic chemicals can lead to an increased solnbility of hydrophobic organic contaminants in the aqueous phase and, conse-qnently, to a potential increase in their transport from land surface to groundwater. 

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